Evaluating drug targets through human loss-of-function genetic variation

Vallabh Minikel, Eric; J. Karczewski, Konrad; C. Martin, Hilary; B. Cummings, Beryl; Whiffin, Nicola; Rhodes, Daniel; Alföldi, Jessica; C. Trembath, Richard; A. van Heel, David; J. Daly, Mark; Aggregation Database Production Team, Genome; Alföldi, Jessica; M. Armean, Irina; Banks, Eric; Bergelson, Louis; Cibulskis, Kristian; L. Collins, Ryan; M. Connolly, Kristen; Covarrubias, Miguel; B. Cummings, Beryl; J. Daly, Mark; Donnelly, Stacey; Farjoun, Yossi; Ferriera, Steven; Francioli, Laurent; Gabriel, Stacey; D. Gauthier, Laura; Gentry, Jeff; Gupta, Namrata; Jeandet, Thibault; Kaplan, Diane; J. Karczewski, Konrad; M. Laricchia, Kristen; Llanwarne, Christopher; V. Minikel, Eric; Munshi, Ruchi; M. Neale, Benjamin; Novod, Sam; H. O’Donnell-Luria, Anne; Petrillo, Nikelle; Poterba, Timothy; Roazen, David; Ruano-Rubio, Valentin; Saltzman, Andrea; E. Samocha, Kaitlin; Schleicher, Molly; Seed, Cotton; Solomonson, Matthew; Soto, Jose; Tiao, Grace; Tibbetts, Kathleen; Tolonen, Charlotte; Vittal, Christopher; Wade, Gordon; Wang, Arcturus; Wang, Qingbo; S. Ware, James; A. Watts, Nicholas; Weisburd, Ben; Whiffin, Nicola; A. Aguilar Salinas, Carlos; Ahmad, Tariq; M. Albert, Christine; Ardissino, Diego; Atzmon, Gil; Barnard, John; Beaugerie, Laurent; J. Benjamin, Emelia; Boehnke, Michael; L. Bonnycastle, Lori; P. Bottinger, Erwin; W. Bowden, Donald; J. Bown, Matthew; C. Chambers, John; C. Chan, Juliana; Chasman, Daniel; Cho, Judy; K. Chung, Mina; Cohen, Bruce; Correa, Adolfo; Dabelea, Dana; J. Daly, Mark; Darbar, Dawood; Duggirala, Ravindranath; Dupuis, Josée; T. Ellinor, Patrick; Elosua, Roberto; Erdmann, Jeanette; Esko, Tõnu; Färkkilä, Martti; Florez, Jose; Franke, Andre; Getz, Gad; Glaser, Benjamin; J. Glatt, Stephen; Goldstein, David; Gonzalez, Clicerio; Groop, Leif; Haiman, Christopher; Hanis, Craig; Harms, Matthew; Hiltunen, Mikko; M. Holi, Matti; M. Hultman, Christina; Kallela, Mikko; Kaprio, Jaakko; Kathiresan, Sekar; Kim, Bong-Jo; Jin Kim, Young; Kirov, George; Kooner, Jaspal; Koskinen, Seppo; M. Krumholz, Harlan; Kugathasan, Subra; Heon Kwak, Soo; Laakso, Markku; Lehtimäki, Terho; J. F. Loos, Ruth; A. Lubitz, Steven; C. W. Ma, Ronald; G. MacArthur, Daniel; Marrugat, Jaume; M. Mattila, Kari; McCarroll, Steven; I. McCarthy, Mark; McGovern, Dermot; McPherson, Ruth; B. Meigs, James; Melander, Olle; Metspalu, Andres; M. Neale, Benjamin; M. Nilsson, Peter; C. O’Donovan, Michael; Ongur, Dost; Orozco, Lorena; J. Owen, Michael; N. A. Palmer, Colin; Palotie, Aarno; Soo Park, Kyong; Pato, Carlos; E. Pulver, Ann; Rahman, Nazneen; M. Remes, Anne; D. Rioux, John; Ripatti, Samuli; M. Roden, Dan; Saleheen, Danish; Salomaa, Veikko; J. Samani, Nilesh; Scharf, Jeremiah; Schunkert, Heribert; B. Shoemaker, Moore; Sklar, Pamela; Soininen, Hilkka; Sokol, Harry; Spector, Tim; F. Sullivan, Patrick; Suvisaari, Jaana; Shyong Tai, E.; Ying Teo, Yik; Tiinamaija, Tuomi; Tsuang, Ming; Dan Turner, Teresa; Tusie-Luna, Teresa; Vartiainen, Erkki; P. Vawter, Marquis; S. Ware, James.; Watkins, Hugh; K. Weersma, Rinse; Wessman, Maija; G. Wilson, James; J. Xavier, Ramnik; L. Schreiber, Stuart; G. MacArthur, Daniel

doi:10.1038/s41586-020-2267-z

Public

Evaluating drug targets through human loss-of-function genetic variation

Published in Nature • May 27, 2020

Authors:

Eric Vallabh Minikel

Konrad J. Karczewski

Hilary C. Martin

Abstract

Naturally occurring human genetic variants that are predicted to inactivate protein-coding genes provide an in vivo model of human gene inactivation that complements knockout studies in cells and model organisms. Here we report three key findings regarding the assessment of candidate drug targets us...

Subject

Human genetic variation

Biology

Computational biology

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